Cerebral ischemia can result in varying degrees of tissue damage. Conditions of severe ischemia can produce irreversible injury, whereas in conditions of moderate ischemia, tissue damage may be reversible. The reversibility of tissue damage—i.a. in the striatum—is important for the development of new therapeutic approaches for treatment.
In connection with an incidence of cerebral ischemia, an excessive amount of glutamate is released from the cortex to the striatum resulting in an excessive depolarization of dopaminergic nerve terminals primarily mediated by sodium influx. This depolarization results in a massive efflux of dopamine, which in turn exerts a neurodegenerative effect in the striatum.
Compounds capable of reducing the striatal dopamine level in such situations would therefore be considered useful for the treatment treatment of diseases associated with reduced blood flow to the brain or with instances of a temporary break in blood supply to the brain, such as ischemic diseases.
It has been mentioned that dopamine release mediated by reversal of the dopamine transporter (DAT) may also be of importance in ischemic conditions in the striatum such that a part of the neurodegenerative changes in the striatum following ischemia results from dopamine release mediated by the dopamine transporter (Leviel V, Neurochemistry International, 38, 83-106, 2001).